α-Dystrobrevin knockout mice have increased motivation for appetitive reward and altered brain cannabinoid receptor 1 expression.

Autor: Hawkes CA; Division of Biomedical and Life Sciences, Lancaster University, Lancaster, UK. c.hawkes@lancaster.ac.uk.; School of Life, Health and Chemical Sciences, Open University, Milton Keynes, UK. c.hawkes@lancaster.ac.uk., Heath CJ; School of Life, Health and Chemical Sciences, Open University, Milton Keynes, UK., Sharp MM; Clinical and Experimental Sciences, University of Southampton, Southampton, UK.; Biomedical Imaging Unit, University Hospital Southampton NHS Trust, Southampton, UK., Górecki DC; Molecular Medicine, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK., Carare RO; Clinical and Experimental Sciences, University of Southampton, Southampton, UK.
Jazyk: angličtina
Zdroj: Acta neuropathologica communications [Acta Neuropathol Commun] 2022 Aug 31; Vol. 10 (1), pp. 127. Date of Electronic Publication: 2022 Aug 31.
DOI: 10.1186/s40478-022-01434-4
Abstrakt: α-Dystrobrevin (α-DB) is a major component of the dystrophin-associated protein complex (DAPC). Knockout (KO) of α-DB in the brain is associated with astrocytic abnormalities and loss of neuronal GABA receptor clustering. Mutations in DAPC proteins are associated with altered dopamine signaling and cognitive and psychiatric disorders, including schizophrenia. This study tested the hypothesis that motivation and associated underlying biological pathways are altered in the absence of α-DB expression. Male wildtype and α-DB KO mice were tested for measures of motivation, executive function and extinction in the rodent touchscreen apparatus. Subsequently, brain tissues were evaluated for mRNA and/or protein levels of dysbindin-1, dopamine transporter and receptor 1 and 2, mu opioid receptor 1 (mOR1) and cannabinoid receptor 1 (CB1). α-DB KO mice had significantly increased motivation for the appetitive reward, while measures of executive function and extinction were unaffected. No differences were observed between wildtype and KO animals on mRNA levels of dysbindin-1 or any of the dopamine markers. mRNA levels of mOR1were significantly decreased in the caudate-putamen and nucleus accumbens of α-DB KO compared to WT animals, but protein levels were unaltered. However, CB1 protein levels were significantly increased in the prefrontal cortex and decreased in the nucleus accumbens of α-DB KO mice. Triple-labelling immunohistochemistry confirmed that changes in CB1 were not specific to astrocytes. These results highlight a novel role for α-DB in the regulation of appetitive motivation that may have implications for other behaviours that involve the dopaminergic and endocannabinoid systems.
(© 2022. The Author(s).)
Databáze: MEDLINE
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